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Vol. 18, Issue 11, 4397-4404, November 2007

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Functional Characterization of the OFD1 Protein Reveals a Nuclear Localization and Physical Interaction with Subunits of a Chromatin Remodeling Complex

Giovanna Giorgio^*, Mariaevelina Alfieri^*, Clelia Prattichizzo^*, Alessandro Zullo^*, Stefano Cairo^*,, and Brunella Franco^*,

*Telethon Institute of Genetics and Medicine, 80131 Naples, Italy; and Medical Genetics, Department of Pediatrics, Federico II University, 80131 Naples, Italy

Submitted March 2, 2007; Revised August 9, 2007; Accepted August 17, 2007
Monitoring Editor: Wendy Bickmore

Oral-facial-digital (OFD) type I syndrome is an X-linked dominant disease (MIM311200) characterized by malformations of oral cavity, face, and digits and by cystic kidneys. We previously identified OFD1, the gene responsible for this disorder, which encodes for a centrosomal protein with an unknown function. We now report that OFD1 localizes both to the primary cilium and to the nucleus. Moreover, we demonstrate that the OFD1 protein is able to self-associate and that this interaction is mediated by its coiled-coil rich region. Interestingly, we identify an OFD1-interacting protein RuvBl1, a protein belonging to the AAA⁺-family of ATPases, which has been recently associated to cystic kidney in zebrafish and to ciliary assembly and function in Chlamydomonas reinhardtii. We also provide experimental evidence that OFD1, together with RuvBl1, is able to coimmunoprecipitate with subunits of the human TIP60 histone acetyltransferase (HAT) multisubunit complex. On the basis of these results, we hypothesize that OFD1 may be part of a multi-protein complex and could play different biological functions in the centrosome-primary cilium organelles as well as in the nuclear compartment.

Present address: Unite d'Oncogenese et Virologie Moleculaire, Institut Pasteur and INSERM U579, 28 rue du Dr. Roux, 75015 Paris, France.

Address correspondence to: Brunella Franco (franco{at}tigem.it)